Pan Ling, Zhang Xue-Jun, Niu Zhi-Yun, Suo Xiao-Hui, Zhang Jing-Yu, Yang Lin, Liu Xiao-Jun, Qiao Shu-Kai, Dong Zuo-Ren, Ohno Ruzo
Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006 Jun;14(3):501-7.
Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC-restricted cytotoxic activity of NK cells and facilitate specific allogeneic human cytotoxic T lymphocyte responses against fresh leukemia cells and cell lines. The Wilms' tumor gene, WT1 mRNA, has been used as a marker of minimal residual disease (MRD) for evaluating therapeutic efficacy of patients with leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate whether in vitro IL-12 can lower WT1 gene expression in peripheral blood monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30 patients and 5 healthy volunteers were cultured at 5 x 10(5) cells/ml alone with or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in 6 CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 may be of considerable benefit in the elimination of MRD in patients with hematological malignancies.
先前的研究表明，白细胞介素-12（IL-12）可增强自然杀伤细胞（NK细胞）的非主要组织相容性复合体（MHC）限制性细胞毒性活性，并促进特异性同种异体人细胞毒性T淋巴细胞对新鲜白血病细胞和细胞系的反应。威尔姆斯瘤基因（WT1 mRNA）已被用作微小残留病（MRD）的标志物，用于评估白血病或骨髓增生异常综合征（MDS）患者的治疗效果。本研究旨在探讨体外IL-12是否能降低白血病或MDS患者外周血单个核细胞（PBMNC）中WT1基因的表达。将这30例患者和5名健康志愿者的PBMNC以5×10⁵个细胞/毫升的浓度单独培养，分别添加或不添加100单位/毫升的IL-12，培养3天。由于WT1 mRNA被认为是白血病和MDS中微小残留病（MRD）的标志物，因此通过竞争性逆转录聚合酶链反应（RT-PCR）来检测WT1 mRNA。结果表明，5名健康志愿者的PBMNC中WT1 mRNA低于10³拷贝/微克总RNA。经过3天的IL-12处理后，6例慢性粒细胞白血病（CML）患者的PBMNC中WT1 mRNA的平均值从10⁴.⁸降至10⁴.²拷贝/微克总RNA，12例MDS患者从10⁵.⁴降至10⁴.⁸拷贝/微克，5例处于完全缓解（CR）的急性髓系白血病（AML）患者从10⁵.⁰降至10⁴.²拷贝/微克，但7例未处于CR的AML患者中有5例未降低。结论是，IL-12可显著降低大多数MDS、CML和处于CR的AML患者PBMNC中的白血病细胞数量。IL-12在消除血液系统恶性肿瘤患者的MRD方面可能具有相当大的益处。
